What is Multiple Sclerosis (MS)?

by | Neurological

Multiple Sclerosis

Sudarshini Ramanathan

Neurologist and clinician-scientist

With World MS Day coming up on Tuesday 30 May 2023, we invite neurologist and clinician-scientist Associate Professor Sudarshini Ramanathan from the University of Sydney, Concord Hospital and the Kids Neuroscience Centre in Sydney to answer some of your most common questions about Multiple Sclerosis (MS).  

What is MS and what are the most common signs and symptoms? How many Australians are affected? 

Multiple sclerosis (MS) is a demyelinating disorder. The immune system targets myelin, the insulating layer that covers nerve fibres, resulting in inflammatory damage to this layer. This causes problems in communicating signals between the brain and the rest of your body. MS can affect all parts of the central nervous system – this can include the brain, the spinal cord, and the optic nerves. In 2023, it is estimated over 33,000 Australians live with MS1

How are people most likely to discover they have MS? 

Patients’ symptoms are related to which parts of the central nervous system are affected by MS and can vary greatly between patients. When this involves the brain, this can result in loss of function, or impaired function, of the parts of the brain affected – sometimes this may present as altered sensations, numbness or tingling, weakness, speech problems, or vertigo. When this affects the spinal cord, this can similarly result in electric shock sensations with neck movements, weakness or loss of sensation in the arms or the legs, lack of coordination, bladder or bowel dysfunction, or pain. When MS affects the optic nerves, this can present as pain with eye movement, and loss of vision including loss of colour vision.

Often what can be very challenging in the management of MS are the ‘invisible’ symptoms such as problems with cognition, mood, fatigue and pain – these are often symptoms that people with MS find very debilitating.

How is Multiple Sclerosis diagnosed? 

Taking a patient’s history and clinical examination help doctors identify what might be in keeping with a possible diagnosis of MS. Magnetic resonance imaging (MRI) scans of the brain, spinal cord, and/or optic nerves are a key investigation to help identify whether areas of damage to the white matter are present in what is a typical distribution for MS. MRI can also help identify atypical features which might suggest a particular patient has another non-MS cause for their presentation.

Patients may undergo a lumbar puncture, where a small volume of fluid around the spinal cord is collected. Analysis of this cerebrospinal fluid may help with diagnosis as many MS patients have particular antibody production in this fluid and this can facilitate diagnosis.

To meet the diagnostic criteria for MS, there must be evidence of disease activity having occurred at different times and different locations in the central nervous system.

Sometimes it is helpful to look for evidence of past damage to the central nervous system – that is, to look for clinically silent involvement of the optic nerves and spinal cord, using neurophysiological tests called evoked potentials. Blood tests may be performed to exclude other mimic disorders.

What is MS?

Who is most likely to be diagnosed with Multiple Sclerosis and at what age? 

MS is about three times more common in women than men. Most patients are diagnosed as young adults in their 20s to 40s. There is certainly a large age range, and patients can be diagnosed as adolescents, or older adults, but this is less common. There is evidence that there is a higher incidence of MS in people born at latitudes further away from the equator.

What are the risk factors? 

MS is an interesting condition as there are many pathways which lead to the development of MS. That is, disease pathogenesis in this condition is thought to be quite multifactorial.

There is a known genetic susceptibility, or human leucocyte antigen (HLA) association which occurs in many patients with MS. This genetic variant called HLA-DRB1*15:01, confers a more than 3 times greater risk of developing MS compared to those who do not have this HLA profile. However, this HLA association in isolation does not cause MS, but rather works with a number of other risk factors to increase your chance of developing MS, as discussed below. 

Some of the identified risk factors suggests that exposure to ultraviolet (UV) radiation may reduce the risk of MS. Increased vitamin D levels and sun exposure during childhood are associated with a reduced risk of MS later in life. Low sun exposure in mothers during the first trimester of pregnancy can be associated with an increased risk of MS in their children. 

A higher body mass index during adolescence in women is also linked to an increased risk of developing MS. Smoking has been established as a risk factor for development of and progression of MS. There is increasing evidence that almost all patients with MS have had a preceding infection, at some stage, with Epstein Barr Virus (EBV). As a large proportion of the general population has had an EBV infection, this is not enough in isolation to cause MS, but likely works in concert with a number of other risk factors to result in the onset of MS. 

What medications/treatments are available for people living with MS? 

Over the past 15 years, there have been great advances in developing multiple treatment options for patients with MS. 

Previously, the mainstay of treatment were injectable options including interferons and glatiramer acetate. These agents are helpful in reducing the risk of relapse by about 30-40% but require ongoing self-administration of injections. The identification of oral treatments such as fingolimod, dimethyl fumarate, and cladribine marked the availability of treatments which can reduce the risk of relapse by 50-70% and may be suited for patients who do not want to self-inject. High efficacy therapy, including natalizumab (monthly infusions), ocrelizumab (six monthly infusions), and alemtuzumab (annual infusion schedule for two to three years), are treatments which can reduce relapse rates by 70-90% and are administered via infusions. 

Today, there are 17 different therapies approved, including oral therapies, as well as infusion therapies. Many of these treatments target different parts of the immune system.

Risks of treatment are unique to each agent and may include an increased risk of infections and other systemic side effects. Decisions related to treatment are made by the neurologist and patient in collaboration after reviewing the risk benefit ratio – that is, what is the risk of disease activity versus the side effect profile of the treatment. Patients who are diagnosed in the modern era have a hugely improved chance of living a normal life with fulfilment at home, work, and with their lifestyle.

What impact can lifestyle have on Multiple Sclerosis? 

General wellbeing is critical in improving outcomes. Some factors that have been identified as beneficial in MS include maintaining a healthy diet and exercise regime to ensure an appropriate weight and lipid profile, as well as the impact on gut health, and cardiovascular health. Exercise is linked with improved physical health, as well as improved cognition and fatigue in MS. Smoking cessation is beneficial in immune mediated disease, and smoking is associated with increased progression in MS as well as worse cardiovascular outcomes like heart attacks and strokes. Quitting smoking at any stage is beneficial.

How can a GP help if I’m worried about having MS?

If you or your loved ones are worried about symptoms you feel are concerning for MS, it’s always important not to carry this burden on your own. See your GP, who may be able to help reassure you if the symptoms and examination are not suggestive of MS or look for alternate explanations of your symptoms.  If they feel the symptoms are indeed concerning for MS, your GP can assist with getting you linked up to a neurologist. With MS, there is good evidence that the sooner this condition is diagnosed and treated, the less inflammatory damage you sustain, and the better outcomes are.

What does the future hold for Multiple Sclerosis research and treatment? 

MS has been an enigma for many decades because there is no clear single causative pathway. There are multiple risk factors, multiple potential contributors, and understanding how these factors are interrelated is critical. It is exciting to observe research that further explains why certain patients develop MS, how certain factors may trigger a more or less severe form of the condition, and how we can target treatments to have the most direct action on these pathways.

While we now have a number of treatment options in relapsing forms of MS, a real area of need is progressive MS. While we have come far in the field, there is a long way to go with understanding how and why patients develop progressive MS, and how best to treat these patients to slow or halt progression. I believe this is, and will continue to be, an important focus in MS research.

To try and address this great unmet need for effective treatments for progressive MS, critical research and clinical trials are underway to find therapies to repair damaged nerves. 

What do Australians need to know about MS?

I would like people living with MS to know that their input and contribution to improving the future is critical. I would like people living with MS to know that researchers deeply value their thoughts on research priorities, study design, and what are the clinical trials that need doing. Reaching out to sources such as MS Australia is a good way to stay on top of opportunities where researchers are keen for patients’ unique insights.

Find out more about MS through https://www.msaustralia.org.au/

REFERENCES


MS Australia Research Advocacy Cure. Multiple sclerosis rising and accelerating in Australia new data shows [Internet]. 2023 [cited 2023 May 30]. Available from https://www.msaustralia.org.au/news/multiple-sclerosis-rising-and-accelerating-in-australia-new-data-shows/